1. Field of the Invention
The present invention relates to compositions containing sphingosylphosphorylcholine and the use thereof as a cellular growth factor.
2. Description of the Background
The biochemical mechanisms whereby eukaryotic cells regulate their proliferation are not well understood. However, an attempt has been made to approach this problem by identifying the second messengers responsible for initiating the progression of G.sub.o -arrested cells into the S phase. In Swiss 3T3 cells, which are sensitive to a wide variety of mitogenic agents, some growth factors appear to function through conventional second messengers such as cAMP, whereas others use the signal pathways associated with increased degradation of polyphosphoinositides leading to the generation of lipid second messengers. Diacylglycerol (DAG) is an endogenous activator of protein kinase C and inositol triphosphate (IP.sub.3) causes a release of Ca.sup.+2 from intracellular stores. Although the roles of these intracellular second messengers have been well characterized, not all of the second messenger systems involved in cell growth regulation have been elucidated. In particular, it is clear that the early responses of quiescent cells to a variety of growth factors,such as changes in Ca.sup.+2 and pH.sub.i, and activation of phospholipase C and protein kinase C, are insufficient by themselves to cause the cells to initiate DNA synthesis. Thus, there are clearly some undiscovered intracellular second-messenger pathways which are important for cell growth regulation.
The present inventors recently discovered that sphingosine at low concentrations stimulates cell proliferation of quiescent 3T3 fibroblasts via a protein kinase C-independent pathway. See Spiegel, S. et al, J. Biol. Chem. 265, 76-81 (1990). The present inventors have also recently demonstrated that the mitogenic effect of sphingosine is mediated by a rapid rise in the levels of phosphatidic acid and of sphingosine-1-phosphate which are both potent mitogens for 3T3 cells. See Spiegel, S., J. Biol. Chem. 265, 21309-21316 (1990) and Spiegel, S. et al, J. Cell Biol. 114, 155-167 (1991).
However, a need exists for mitogenic compounds of increased potency which have little or no loss of cell viability associated therewith.